Improved survival in metastatic breast cancer: results from a 20-year study involving 1033 women treated at a single comprehensive cancer center.

PURPOSE: Diagnosis and treatment of breast cancer have changed profoundly over the past 25 years. The outcome improved dramatically and was well quantified for early stage breast cancer (EBC). However, progress in the treatment of metastatic disease has been less convincingly demonstrated. We have studied survival data of patients with metastatic breast cancer (MBC) from a large academic cancer center over a period of 20 years. METHODS: Data from 1033 consecutive MBC patients who were treated at the Department of Medical Oncology of the West German Cancer Center from January 1990 to December 2009 were retrospectively analyzed for overall survival (OS) and risk factors. Patients were grouped in 5-year cohorts, and survival parameters of each cohort were compared before and after adjustment for risk factors. RESULTS: Overall survival of patients with MBC treated at specialized center has significantly improved from 1990 to 2010 (hazard ratio 0.7, 95%CI 0.58-0.84). The increments in OS have become less profound over time (median OS 1990-1994: 24.2 months, 1995-1999: 29.6 months, 2000-2004: 36.5 months, 2005-2009: 37.8 months). CONCLUSION: Survival of patients with MBC has improved between 1990 and 2004, but less from 2005 to 2009. Either this suggests an unnoticed shift in the patient population, or a lesser impact of therapeutic innovations introduced in the most recent period.

Preemptive tumor profiling for biomarker-stratified early clinical drug development in metastatic breast cancer patients.

Biomarker-stratified cancer pharmacotherapy was pioneered in the care of breast cancer patients. The utility of agents modulating hormone receptors, synthesis of steroid hormones, or HER2-targeting agents has been greatly enhanced by the detection of predictive biomarkers in diagnostic tumor samples. Based on deeper understanding of breast cancer biology multiple drug candidates have been developed to modulate additional molecular targets which may associate with specific biomarker profiles. Accordingly, exploratory biomarkers are increasingly incorporated in early clinical trials, thus demanding a new process of patient selection. Here, we describe the implementation of preemptive, multiplexed biomarker profiling linked to standard diagnostic algorithms for metastatic breast cancer patients treated at the West German Cancer Center. Profiling for experimental biomarkers was prospectively offered to patients with metastatic breast cancer who met generic clinical trial inclusion criteria. Formalin-fixed, paraffin-embedded tumor samples were retrieved and studied for potentially "actionable" biomarkers related to active clinical trials by immunohistochemistry, amplicon sequencing, and in situ hybridization. The clinical course of those "profiled" patients was closely monitored to offer trial participation whenever applicable. Here, we report results from the first 131 patients enrolled in this program. PIK3CA mutations (23 %) and amplifications (2 %), loss of PTEN expression (13 %), and FGFR1 amplifications (8 %) were detected next to established biomarkers such as estrogen (67 %) and progesterone receptor expression (52 %), and HER2 overexpression or amplification (23 %). So far 16 "profiled" patients (12 %) have been enrolled in biomarker-stratified early clinical trials. Preemptive profiling of investigational biomarkers can be integrated into the diagnostic algorithm of a large Comprehensive Cancer Center. Extensive administrative efforts are required to successfully enroll "profiled" patients with metastatic breast cancer in early clinical trials stratified by exploratory biomarkers.